INVESTIGATION OF CYTOTOXIC AND APOPTOTIC EFFECTS OF PRANGOS HEYNIAE H. DUMAN & M. F. WATSON EXTRACTS ON HEPG2 CELLS

Abstract

Objective: This study aims to investigate the anticancer potential of Prangos Heyniae H. Duman & M. F. Watson root extracts against human hepatoma cells, and examine the molecular mechanisms potentially involved in extract-induced cytotoxicity. Material and Method: HepG2 cells were treated with chloroform, n-hexane, or methanol extracts from roots of P. heyniae to investigate the possible effects on cell viability. Following the determination of IC50 values by the MTT test, n-hexane, and methanol extracts were excluded because of their selectivity indices. The chemical characterization of chloroform extract was performed by HPLC to understand the chemical composition-bioactivity relationship. Alterations induced by chloroform extract on mitochondrial membrane potential and caspase-3 activation were further investigated. In addition, cell viability was measured in the presence of different selective inhibitors of pathways to define the type of cell death pathway contributing to cytotoxicity. Result and Discussion: Chloroform extract but not n-hexane or methanol extracts led to strong and selective inhibition of cell viability on HepG2 cells. In addition, cytotoxicity increased by chloroform extract was only restored in the presence of a pan-caspase apoptosis inhibitor. Also, treatment of HepG2 cells with chloroform extract impaired mitochondrial membrane potential and led to significant caspase-3 activation. Oxypeucedanin, isoimperatorin, and osthole were detected as the major components of the chloroform extract. These results represent that apoptosis may be involved in the anticancer effect of coumarin and furanocoumarin derivatives in chloroform extract.